Ch 15 Antimicrobial Drugs

Alexander Fleming

• Discovered one of his culture plates was contaminated w moold that produced a compound that inhibited the bacteria

  • named penicillin

• Indentified cultured plates

broad-spectrum drugs

• effective against both gram-positive and gram negative bacterial cell

  • quinolones → ciprofloxacin & levofloxacin

narrow spectrum drugs

• target a limited range of bacteria

  • bacitracin & vancomycin are mainly effective against gram pos species

bacteriostatic

• prevent bacteria from growing

  • typically target protein synthesis and metabolic pathways

bactericidal

• actively kill bacteria

  • target bacterial cell walls or cell membranes and nucleic acids

antibiotics

naturally occurring antimicrobial compounds

synthetic antimicrobials

• manufactured by chemical processes

  • one option for overcoming antibiotic-resistance mechanisms

    • ex: prontosil

semisynthetic antimicrobials

naturally occurring antibiotics that are chemically modified to improve stability or pharmacological actions

selective toxicity

inhibits or kills target microbe without damaging host cells

therapeutic index

• ratio of maximum safe dose over minimum effective dose

• drugs w high therapeutic index is effective well below the dose at which it is toxic- safe drug

nephrotoxic

kidney toxic

ex: aminoglycosides

hepatotoxic

liver toxic

drug-induced liver injury

ex: amoxicillin-clavulanate

beta-lactam antimicrobials

• superfamily of antibacterial drugs

• block cell wall construction

• work by binding transpeptidase enzymes

  • these enzymes form protein cross links that bind peptidoglycan chains together

beta-lactamases

enzymes produced by bacteria that inactivate beta-lactam drugs

beta-lactamse inhibitors

co-administered w certain beta-lactam drugs to combat beta-lactamases

cephalosporins

• broad-spectrum and bactericidal

• exist naturally & have been semisynthetically derived

• largest collection of beta-lactam drugs

• pt w penicillin allergies may have a cross-rxn to first generation cephalosporins (similar in structure)

carbapenems

• broad-spectrum

• effective against a variety of multidrug-resistant strains

• incidence of allergy is low

• only injectable forms

monobactams

• narrow-spectrum

• effective against gram-negative bacteria

  • Pseudomonas, Klebsiella, Proteus, and Enterobacter

• not useful against gram-positive bacteria

• one ring in their structure

• one drug for humane use: aztreonam

• can usually be used in penicillin-allergic patients

glycopeptides

• non-beta-lactam drug that targets cell wall construction

• narrow-spectrum

• effective against gram positive organisms and some resistant strains

• red man syndrome

  • side effect of red flush spreading over skin

• ex: teicoplanin & vancomycin

quinolones

• synthetic antimicrobials that target DNA replication enzymes

  • DNA gyrase and topoisomerases

• broad-spectrum

• long half-life

rifamycins

• originally isolated from bacteria- mainly produced as synthetic or semisynthetic compounds

• rifampin

• broad-spectrum

• effective against most gram-pos and some gram neg bacteria

• inhibits transcription by binding to RNA pol

macrolides

• broad spectrum

• effective against gram neg cocci, aerobic & anaerobic gram post rods & cocci

lincosamides

• broad spectrum

• effective against aerobic & anaerobic gram pos & anaerobic gram neg bacteria & some protozoans

phenicols

• bind to 50S ribosomal subunit

• chloramphenicol

• effective against gram pos & gram neg cocci & bacilli

• narrow therapeutic index

• associated w bone marrow toxicity that causes aplastic anemia

• reserved for treating sever multidrug-resistant infections

tetracyclines

• family of chemically-related broad-spectrum bacteriostatic drugs

• bind to 30S ribosomal subunit

• associated w increased risk of c. difficile infection

• side effect include:

  • photosensitivity

  • detrimental effects on bone & teeth in children under 8

aminoglycosides

• collection of mainly narrow spectrum drugs

• bind to 30S ribosomal subunit

• poorly absorbed in the intestinal tract - half life of 2-3hrs

  • usually given IV instead

• effective against gram neg aerobic & facultative anaerobic bacilli - like p. aeruginosa

• typically used in combination therapy w beta-lactams

albendazole

• broad spectrum

• interfere w glucose uptake by targeting microtubules

• treat a collection of roundworms & tapeworms

praziquantel

• fluke and tapeworm infection

• paralyzes parasites & causes them to release attachment & are expelled

kirby-bauer test

• zone of inhibition may be seen if the bacteria are prevented from growing

• drug kills bacteria or stops it from growing

E-test

• strip w a variable gradient of drug placed on agar plates

• minimal inhibitory concentration (MIC)

  • lowest concentration of antimicrobial drug that inhibits the microbe’s growth

  • MIC is the point where the zone of inhibition begins

minimum bactericidal concentration (MCB)

concentration of drug that kills 99.9% of the bacteria present

antimicrobial resistance

• defined as a situation in which a microbe (bacterium, virus, fungi, protozoan or helminth) is not affected by drug therapy that is intended to inhibit or eliminate the pathogen

superbug

resistant microbes that are unaffect by treatment and increase numbers causing a superinfection

intrinsic resistance

• natural resistance

• rarely provides full protection but makes certain pathogen more difficult to eliminate

acquired resistance

• emergence of “resistant strains”

• genetic mutation or transfer of drug-resistance gene

• HGT

A 6-year-old patient is suffering from Lyme disease, and antimicrobials are prescribed to treat the infection. Which of the following antimicrobial compounds would not be prescribed?

tetracyclines

What are the three main ways microbes evade antimicrobial drugs?

• Pump drugs out

• Inactivate drugs

• Alter drug target sites

___________ is the minimum concentration of the drug that kills at least 99.9 percent of the bacteria present.

MBC- minimum bactericidal concentration

Neosporin is a topical antimicrobial ointment that is commonly applied to minor scrapes and burns. It contains the antimicrobial agent neomycin. Neomycin is a member of the __________.

aminoglycoside class.

Antivirals do not target __________.

viral ribosomes

Antibiotics are _________________.

naturally occurring antimicrobial compounds

Which of the following antibacterial drugs targets the cell wall of bacteria?

Vancomycin

In the __________, paper disks impregnated with antibiotics are added to a solid medium inoculated with a standard amount of a pure bacterial culture to test whether the organism is sensitive, intermediate, or resistant to the drug.

kirby-bauer test

Most cases of Clostridioides difficile infections have been preceded by a prolonged treatment with __________.

broad-spectrum antimicrobial drugs